Macaques immunized with uninfected human cells have been shown to be protected from challenge with SIV propagated in human cells. To identify the potential antigens involved in this protection, macaques were immunized with uninfected human cells (HuT 78/H9), beta-2 microglobulin, and HLA Class I and Class II proteins purified from these human cells. Although all macaques developed high antibody titers to the proteins with which they were immunized, only macaques immunized with Class II protein (HLA-DR) developed antibodies to Class II and were protected from an intravenous virus challenge. These results were the first demonstration that immunization with a purified cellular protein can protect from virus infection (L. Arthur et al., J Virol 69:3117-3124, 1995). In collaboration with Dr. Gaur we identified class II alleles in the pig-tailed macaque colony and purified class II DR using the same techniques that lead to the purification of HLA DR. Macaques that share s imilar and distinct class II alleles (as determined by Dr. Gaur) will be immunized with this purified DR and then challenged with SIVMne grown in lymphocytes from the animal from which the class II antigen was purified. These studies will further address whether antibodies to class II correlate with protection from infection in an alloimmunization regimen, and may help explain why there is resistance to infection in some cohorts (prostitutes in Gambia, for example). The results of this study may also be applicable to AIDS vaccine design. Four macaques were used in a titration of the challenge virus. Two macaques each received 10-3 and 10-4 TCID intravenously in August 1998. In November 1998 the remaining 6 macaques began the DR immunization protocol. FUNDING NIH grant RR00166 and SAIC (Science Applications International Corp.) grant 97CYS0192A.